The Nathan Shock Aging Center will build upon the recognized strengths in basic research in aging at San Antonio, e.g.: (1) the utilization of transgenic animals and dietary restriction to study of the mechanism(s) of aging at the molecular, cellular, and physiological levels, (2) the detailed characterization of survival and pathological lesions in aging rodents to determine the effect of aging, disease, and their interaction on biological processes, and (3) the large number of faculty at San Antonio who are actively involved in basic biological research in aging. The Center proposed in this application will consist of three Resource Cores, a Research Development Core, and a Program Enrichment Core. The Resource Cores will include a Transgenic Core, an Animal Core, and a Pathology Core. The central premise underlying the Nathan Shock Aging Center described in this proposal is that identifying the biological mechanisms leading to senescence can best be achieved by manipulating the whole organism genetically, nutritionally, or pharmacologically in ways that modify the aging process rather than by relying on phenomenological studies of the aging phenotype. The purpose of the Nathan Shock Aging Center is to combine this approach with our existing research strengths to enhance basic research on aging in five ways. First, the Center will facilitate genetic manipulations of animal models to test hypotheses relevant to senescence; services required to produce transgenic mice, transgenic rats, and transgenic mice with gene knockouts will ter investigators. Second, the Center will provide the resources and environment for the development of new genetic, nutritional, and pharmacological interventions in rodent models that are designed to modify the aging process(es). Animals from these interventions will then be supplied to Center investigators to test hypotheses concerning the mechanism(s) of mammalian aging. Third, the center will characterize the pathological status of all animal models developed in the Center. Fourth, the Center will promote novel approaches to the study of aging by providing funds for pilot projects. Fifth, the Center will have an administrative base designed to enhance collaborative research on aging.